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Abstract: The benefit of treating anal precancerous lesions to reduce anal cancer progression was recently shown in people living with HIV. This will certainly impact the future development of recommendations on anal cancer prevention by including anal precancerous lesions screening and treatment for people living with HIV. However, by bringing this topic to the spotlight, it has also uncovered data that are still missing in this field and that need to be addressed by research.This article will discuss the many unanswered questions about treatment of anal precancerous lesions and future directions for research., Competing Interests: The author has declared that there are no conflicts of interest., (Copyright © 2023, ASCCP.)

Appropriate surveillance and treatment of Barrett's esophagus (BE) is vital to prevent disease progression and decrease esophageal adenocarcinoma (EAC)-related mortality. We sought to determine the variation in BE care and identify improvement opportunities. 275 physicians (113 general gastroenterologists, 128 interventional gastroenterologists, 34 gastrointestinal surgeons) cared for 3 simulated patients, one each from 3 BE clinical scenarios: non-dysplastic BE (NDBE), BE indefinite for dysplasia (IND), and BE with low grade dysplasia (LGD), and care scores were measured against societal guidelines. Overall quality-of-care scores ranged from 17% to 85% with mean of 47.9% ± 11.8% for NDBE, 50.8% ± 11.7% for IND, and 52.7% ± 12.2% for LGD. Participants appropriately determined risk of progression 20.3% of the time: 14.4% for NDBE cases, 19.9% for LGD cases, and 26.8% for IND cases (P = .001). Treatment and follow-up care scores averaged 12.9% ± 17.5% overall. For the LGD cases, guideline-recommended twice-daily PPI treatment was ordered only 24.7% of the time. Guideline-based follow-up endoscopic surveillance was done in only 27.7% of NDBE cases and 32.7% of IND cases. For the LGD cases, 45.4% ordered endoscopic eradication therapy while 25.1% chose annual endoscopic surveillance. Finally, participants provided counseling on lifestyle modifications in just 20% of cases. Overall care of patients diagnosed with BE varied widely and showed room for improvement. Specific opportunities for improvement were adherence to guideline recommended surveillance intervals, patient counseling, and treatment selection for LGD. Physicians would potentially benefit from additional BE education, endoscopic advances, and better methods for risk stratification., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: Gastric intestinal metaplasia (GIM) is an attractive target for surveillance and treatment as it can progress to gastric adenocarcinoma (GAC). Yet, GIM remains a challenging area for clinicians as most patients do not progress to cancer, and there are conflicting data regarding the benefits of surveillance and therapy. This review aims to summarize recently published GIM surveillance guidelines, to discuss, which patients with GIM may benefit from treatment, and to review pivotal and recent literature on GIM therapy., Recent Findings: Guidelines published by American, British, and European gastroenterology societies do not recommend universal surveillance, but do suggest endoscopic surveillance in patients with risk factors for progression to GAC. Although light examination for at least 7 min and mapping biopsies may increase yield for dysplasia and GAC. In randomized trials, Helicobacter pylori eradication reduced risk of dysplasia and cancer. In GIM with visible dysplasia and early-stage GAC, endoscopic resection improves quality of life without reducing survival compared with surgery. Endoscopic ablation therapies have shown promise for invisible or extensive dysplasia., Summary: Endoscopic resection is appropriate for visible dysplasia and early-stage GAC without high-risk features that persists despite H. pylori eradication therapy. Prospective studies are needed to assess the utility of endoscopic ablation in GIM., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Gastric cancer is one of the most common malignant tumors, which seriously affect peoples quality of life and threaten people's health. Precancerous lesions of gastric cancer (PLGC) are a critical stage in the occurrence and development of gastric cancer. Early effective intervention is an important means to prevent and control gastric cancer. In this study, we will evaluate the efficacy and safety of complementary and alternative therapies in the treatment of PLGC by Bayesian network meta-analysis (NMA)., Methods: We will search PubMed, Cochrane Library, CNKI and other databases to gather randomized controlled trials (RCTs) on the treatment of PLGC with complementary and alternative therapies. Two reviewers will screen the literature and extract the data according to the inclusion and exclusion criteria, and then assess the quality and bias risk according to Cochrane's Risk of Bias Assessment Tool. Bayesian network meta-analysis will be conducted by Stata16.0 and WinBUGS1.4.3., Results: This study will compare and rank the efficacy and safety of different complementary and alternative therapies for PLGC., Conclusion: This study can provide reliable evidence for the efficacy and safety of complementary and alternative therapies in treatment of PLGC. We expect to provide scientific and rigorous evidence support for clinicians and patients, and then assist them to choose the optimum treatment., Protocol Registration Number: INPLASY2020120077., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Hepatocellular carcinoma (HCC) is a complication of the common genetic condition hereditary hemochromatosis (HH). It is unknown whether HH as an etiology of liver disease impacts the outcome. We compared the results of liver transplantation (LT), surgical resection and locoregional therapies in a matched cohort study and investigated whether HH as an etiology has an impact on survival., Materials and Methods: Consecutive patients with HH and HCC (2000 to 2015) were compared with age, sex and Barcelona Clinic Liver Cancer (BCLC) stage-matched non-HH HCC cases. Patients were offered curative or noncurative treatment according to BCLC stage and Milan criteria. The primary endpoint was all-cause mortality., Results: A total of 102 patients (52 HH; total cohort median age: 67 [44 to 78] y, 97% male, Model for End-stage Liver Disease: 9 [5 to 31]) were studied with a median follow-up of 22 (3 to 126) months. Of the HH cases, the median serum ferritin at diagnosis of HCC was 326 (27 to 5718) μg/L and α-fetoprotein 33 (2 to 197,926) kIU/L. Five-year survival for HH patients receiving curative therapy was 77% (80% for LT, 67% for resection/radiofrequency ablation), and 15% (23% for transarterial chemoembolization) for those undergoing noncurative therapy. Survival for HH patients compared with controls was similar (hazard ratio=0.949; P=0.839). On multivariate Cox regression survival analysis, BCLC stage, and diagnosis of ischemic heart disease (but not HH diagnosis) were independently associated with reduced survival., Conclusions: Patients with HCC and HH can achieve comparable survival rates following curative or LRT modalities to other liver diseases. The BCLC staging system accurately stratifies survival and excellent 5-year survival is possible following LT in selected patients.

Purpose of Review: To identify and review the recent literature on clinical applications, outcome, and new developments in photodynamic therapy (PDT) for the treatment of head and neck cancer., Recent Findings: Although PDT and surgery have a similar local control and recurrence rate, the gold standard of treatment for early-stage oral cavity cancer remains local surgery with, on indication, concurrent treatment of the neck. PDT proves its value in treatment of patients with field cancerization and patients with superficial recurrence after previous surgery and/or radiation, in whom surgical salvage would entail important morbidity. PDT is also promising as an adjuvant treatment after surgery in the presence of macroscopic or microscopic involved margins, in patients where reresection or reirradiation would imply an unacceptable risk. Recent progress in the field of PDT focuses on development and clinical application of new photosensitizing agents, photochemical internalization, and photoimmunotherapy., Summary: The value of PDT in specific well-selected head and neck cancer clinical scenarios is well established. The basic research field is rapidly evolving and experimental findings are promising, maybe eventually leading to optimized results, less side-effects, and more indications.

Objective: The aim of the study was to evaluate the impact of maintenance on performance of cryosurgical equipment used in El Salvador primary health clinics., Materials and Methods: Nine gynecological cryotherapy devices used in El Salvador were bench tested against a new machine of the same make and model. The devices were run for five successive double-freeze cycles. The El Salvador machines then received maintenance by a specialized engineer and another double-freeze cycle was performed. Temperature at the device probe tip was recorded throughout each cycle and ballistic gelatin was used as the tissue analogue to measure freeze ball dimensions achieved by the devices. Outcome measures were mean lowest-sustained temperatures and freeze ball mean weight, depth, and diameter. Paired and unpaired t tests were used to compare results premaintenance versus postmaintenance and postmaintenance versus the reference, respectively., Results: Premaintenance versus postmaintenance freeze ball dimensions were significantly different (mean differences in weight = 2.31 g, p = .01; depth = 2.29 mm, p = .03; diameter = 3.51 mm, p = .02). However, postmaintenance dimensions were not significantly different than those of the reference (weight = 7.44 g vs. 8.39 g, p = .07; depth = 10.71 vs. 11.24 mm, p = .1; diameter = 31.38 mm vs. 32.05 mm, p = .3). Postmaintenance, minimum, and lowest-sustained temperatures were within the recommended clinical range., Conclusions: Specialized maintenance was necessary for heavily used cryotherapy devices to perform adequately, highlighting the challenges of gas-based cryotherapy in low- and middle-income countries.

Serous tubal intraepithelial carcinoma is considered the precursor lesion of high-grade serous carcinoma, and found in both low-risk and high-risk populations. Isolated serous tubal intraepithelial carcinomas in patients with BRCA1/2 mutations are detected in ∼2% of patients undergoing risk-reducing bilateral salpingo-oophorectomy and even with removal of the tubes and ovaries the rate of developing primary peritoneal carcinoma following remains up to 7.5%. Postoperative recommendations after finding incidental STICs remain unclear and surgical staging, adjuvant chemotherapy, or observation have been proposed. Discovery of STIC should prompt consideration of hereditary cancer program referral for BRCA1/2 mutation screening.

Purpose of Review: The purpose of this article is to provide an update on English-language literature evaluating the current understanding of incidence, management, and prevention of vocal fold leukoplakia focusing on premalignancy., Recent Findings: Recent studies have continued to try to elucidate factors influencing recurrence and progression of dysplastic disease, though results vary. Although advanced diagnostic techniques have attempted to predict disease behavior, tissue diagnosis continues to be essential. Studies reinforce the necessity of removal of disease as the primary treatment, whereas use of photoangiolytic lasers via the ablative technique has increased, as has transition of some patients into the office-based settings for treatment. Although genetic and molecular testing may hold promise for predictive purposes, further study is necessary, and chemotherapy for recalcitrant disease continues to be an area of study with few case studies being reported., Summary: Management of vocal fold leukoplakia continues to progress in terms of identification and treatment. Although many work to advance our knowledge in the field and push treatment strategies toward newer avenues, pathologic diagnosis, eradiation of disease on the basis of experience and skill, and close surveillance continue to be paramount.

Percutaneous imaging-guided core needle biopsy (CNB) is a less invasive and less expensive alternative to surgical biopsy for the evaluation of breast lesions. After a CNB the radiologist determine if there is concordance between the pathology, imaging, and clinical findings. Patient management after CNB diagnosis of high-risk breast lesion varies. Surgical excision is warranted for lesions yielding a CNB diagnosis of ADH; however controversy exists regarding the need for surgical excision after CNB diagnosis of radial scar, papillary lesion, atypical lobular hyperplasia (ALH), or lobular carcinoma in situ (LCIS). Repeat CNB or surgical excision is warranted if histologic findings and imaging findings are discordant.

Laryngeal carcinogenesis is a multistep process, characterized by an accumulation of genetic changes associated with architectural and cytologic alterations, ranging from squamous hyperplasia to carcinoma in situ and encompassed by the terminology of squamous intraepithelial lesions (SILs). The etiology, classification, genetic changes, and malignant progression of these lesions are reviewed. Tobacco remains the principal etiological factor with gastroesophageal reflux disease recently considered as a possible factor. In contrast, there is little evidence that microbiological agents, especially human papillomavirus infection, are frequently involved in laryngeal carcinogenesis and probably <10% of SILs are driven by biologically active human papillomavirus infection. Light microscopy, despite a degree of subjectivity, remains the mainstay of accurate diagnosis, prognosis, and guidance for a patient's treatment. The currently used classifications, the dysplasia system, squamous intraepithelial neoplasia, and the Ljubljana classification, reflect different standpoints on this important topic. The modified Ljubljana classification, with good interobserver agreement, could be considered as a proposal for a unified classification of laryngeal SILs. This review also briefly discusses recently discovered genetic changes, such as CDKN2A and CTNNB1 genes, and chromosome instability of chromosomes 1 and 7; however, none of these can at present improve histologic diagnosis. Malignant progression of precursor lesions varies from 2% to 74%, according to different studies. Cold-steel microinstruments, CO2 laser, and radiotherapy are used to treat the different grades of precursor lesions. There is as yet no worldwide agreement on the treatment of high-grade lesions and carcinoma in situ.

Objective: Current guidelines recommend including 13 or 14 high-risk human papillomavirus (HPV) types for triage of atypical squamous cells of undetermined significance (ASC-US) cervical cytology; however, at least 13 additional types are considered possibly oncogenic. We evaluated the effect of including possibly oncogenic HPV types in the test panel., Methods: Outcomes for all women 30 years or older with ASC-US and positive HPV testing who underwent colposcopic biopsy at University of Washington Medical Center-affiliated clinics between 2010 and 2011 were reviewed. We compared biopsy results between cases that were HPV positive for 1 or more of 13 possibly oncogenic types only (26/53/55/62/64/67/69/71/73/82/83/84/IS39) versus 1 or more of the 14 established high-risk types (16/18/31/33/35/39/45/51/52/56/58/59/66/68). We used the Fisher exact test to compare cervical intraepithelial neoplasia grade 2 or higher (CIN2+) diagnoses between HPV risk groups., Results: Three hundred twenty-six ASC-US HPV-positive cervical cytology results were identified, with 170 that were linked to subsequent cervical biopsy results. Among 51 cases positive for possibly oncogenic types only, 31 (61%) had no neoplasia, 20 (39%) had CIN1, and none had CIN2+. Among 119 controls positive for at least one established high-risk type, 64 (53%) had no neoplasia, 42 (35%) had CIN1, and 13 (11%) had CIN2+ (p = .01 for the comparison of CIN2+ diagnoses between groups)., Conclusions: The inclusion of possibly oncogenic types in the HPV test panel led to an additional 51 colposcopy biopsies (33% increase), with no additional cases of CIN 2+. Our results suggest that including possibly oncogenic HPV types increases the number of colposcopy biopsies with minimal improvements in detection of CIN2 +.

Human papillomavirus (HPV) infection of the lower genital tract is common and its effects are variable. The majority of infections are transient and the related pathology is self-resolving. Condyloma accuminatum is caused predominantly by HPV 6, 11 and can be managed with medical or surgical therapy. Vulvar intraepithelial neoplasia is a treatable precursor to vulvar cancer with 2 main forms: one related to HPV and the other to chronic vulvar inflammatory conditions. It may be treated medically, surgically, or potentially via the use of therapeutic HPV vaccines. Preventive utilization of a quadrivalent HPV vaccine has the potential to decrease HPV-related lower genital disease burden substantially.

Endometrial hyperplasia is of clinical significance because it is often a precursor lesion to adenocarcinoma of the endometrium. Making the distinction between hyperplasia and true precancerous lesions or true neoplasia has significant clinical effect because their differing cancer risks must be matched with an appropriate intervention to avoid undertreatment or overtreatment. Pathologic diagnosis of premalignant lesions should use criteria and terminology that clearly distinguish between clinicopathologic entities that are managed differently. At present, the endometrial intraepithelial neoplasia schema is tailored most closely to this objective, incorporating modified pathologic criteria based upon evidence that has become available since the creation of the more widely used 1994 four-class World Health Organization schema (in which atypical hyperplasia is equated with precancerous behavior). The accuracy of dilation and curettage compared with endometrial suction curette in diagnosing precancer and excluding concurrent carcinoma is unclear. Hysteroscopy with directed biopsy is more sensitive than dilation and curettage in the diagnosis of uterine lesions. When clinically appropriate, total hysterectomy for endometrial intraepithelial neoplasia provides definitive assessment of a possible concurrent carcinoma and effectively treats premalignant lesions. Systemic or local progestin therapy is an unproven but commonly used alternative to hysterectomy that may be appropriate for women who are poor surgical candidates or who desire to retain fertility.

Purpose of Review: Endoscopy is the first-line examination and most reliable way to get precise bidimensional assessment of the superficial extent of a squamous cell cancer arising within the upper aerodigestive tract (UADT). Its role as the cornerstone at each diagnostic step in the evaluation of head and neck cancer patients, in both treatment and follow-up, cannot be overemphasized. A number of technological improvements have been introduced to enhance conventional white light endoscopy of the UADT, in order to provide deeper insight into the specific biological properties of observed lesions. The purpose of this review is to summarize the most recent trends in 'biologic endoscopy' techniques., Recent Findings: Starting from the use of toluidine blue up to the most recent light-based detection systems such as autofluorescence and narrow band imaging, researchers have devoted substantial efforts to the identification of specific biological properties of neoplastic tissues that can be targeted by new endoscopic tools. These aids attempt to assist the surgeon in achieving a more reliable distinction between normal and neoplastic or precancerous mucosa, within a wide range of inflammatory and iatrogenic modifications., Summary: Even though direct comparison of the efficacy of these techniques is seldom feasible due to their site-specific application, different advantages and disadvantages, economic considerations, and limited diffusion in daily practice, it is nevertheless clear that the future of endoscopy of the UADT will be strongly influenced by these new technologies.

Acceptance and incorporation of widespread mammographic screening has led to an increase in the incidence of detection of "premalignant" breast lesions. Despite advances in our understanding of these diseases, their actual malignant potential remains somewhat unpredictable. Best current management of these diseases requires a multidisciplinary, coordinated approach between the disciplines of breast surgery, radiology, pathology, medical oncology, and radiation oncology at a minimum. Although this strategy has led to excellent outcomes, future advances in our understanding of the biologic determinants and behavior of these diseases will hopefully result in a more accurate assessment of the risk of progression to invasive breast cancer and allow us to individualize treatment more effectively.

Lymphoid malignancies are rare in patients with Fanconi anemia (FA), particularly after bone marrow transplantation. A boy, who was diagnosed with FA at the age of 5; underwent successful bone marrow transplantation at the age of 11. One year later, he presented with fever and dry cough, and was found to have an anterior mediastinal tumor. Biopsy of the tumor revealed precursor-T cell lymphoblastic lymphoma. Human leukocyte antigen analysis confirmed that the tumor cells were derived from the patient's own cells. He received mild chemotherapy for lymphoma, but his condition deteriorated rapidly and he died from excessive chemotherapy-related toxicity. The literature contains no reports of successful chemotherapy for lymphoid tumors in patients with FA, and therefore, alternatives to chemotherapy should be considered in the treatment of such patients.

Learning Objectives: After reading this article, the participant should be able to: 1. Clinically describe various cutaneous neoplasms. 2. Identify the corresponding histopathologic findings. 3. Discuss the optimal treatment approach for each entity., Summary: Cutaneous neoplasms are broadly viewed as benign, premalignant, or malignant. In dermatology, lesions are classified based on the primary cell of origin or the component of the skin predominantly affected by the pathologic change (epidermis, dermis, or subcutaneous fat). The diagnosis and treatment of skin lesions rely on understanding the clinical presentation and corresponding histopathology. Surgical treatment is not always indicated and is dependent on multiple variables. This review discusses several benign and premalignant neoplasms frequently encountered by the plastic surgeon. The emphasis is on clinical presentation, histopathologic correlation, and management approach.

Purpose of Review: Significant changes in concepts of managing Barrett's esophagus have led to change in the recommendations concerning screening, surveillance, biomarkers, and therapies in this condition over the past several years. We summarize the important changes in this regard., Recent Findings: Narrow band imaging and esophageal capsule endoscopy are alternative methods to screen for Barrett's esophagus. Narrow band imaging provides clear visualization of the mucosal pit patterns and vascular patterns, which improve the diagnostic value for specialized intestinal mataplasia. Esophageal capsule endoscopy is a new potential tool that allows a direct noninvasive visualization of esophagus. Research efforts are currently directed towards risk stratification of patients and biomarkers have been developed to predict development of esophageal adenocarcinoma. Recent studies have reported that frequent loss of heterozygosity (LOH) as well as allelic imbalances in chromosomes in esophageal adenocarcinoma. Fluorescent in-situ hybridization technique, which uses fluorescently labeled DNA probes to detect chromosomal alterations in cells, obtained from cytology specimens has been developed. It showed more sensitive and specific for abnormalities than PCR based techniques. Currently, many studies support the concept of endoscopic elimination of dysplastic lesions in the esophagus by a mucosal ablation therapy. Photodynamic therapy and radiofrequency ablation are recently developed, emerging techniques., Summary: Recent advances in screening; prognostication and therapy for esophageal adenocarcinoma in Barrett's esophagus have brought a significant new insight in clinical practices and will eventually ensure better patients outcomes.

The management of the columnar-lined oesophagus (CLO) has remained controversial for the last 10 years, with practices varying between individual physicians and centres throughout the United Kingdom. Various guidelines exist, although international consensus over issues such as the recognition of short-segment disease and surveillance policies for uncomplicated and dysplastic disease is lacking. Questionnaires examining the practice of diagnosis and surveillance of CLO were sent to 41 centres spread throughout the United Kingdom. Thirty (73%) centres replied. Twelve (40%) had a specific written policy for the management of CLO. Twenty-five (83%) centres made a diagnosis of CLO in the presence of any length of columnarization. Twenty-seven (90%) centres surveyed CLO with 81% of them undertaking a selective surveillance policy. Endoscopic surveillance intervals were fairly consistent for uncomplicated CLO and high-grade dysplasia, but were less consistent for low-grade dysplasia. Results confirmed that even amongst centres with a specialist interest in the management of CLO, marked variations exist in diagnosis and surveillance practice.

Select groups of premalignant oral lesions carry a high risk of development of secondary premalignant lesions and oral squamous cell carcinoma (OSCC). The goal of the present study was to determine the feasibility of using premalignant lesion-pulsed dendritic cells as a treatment option to prevent development of secondary lesions and development of OSCC. Mice that were treated with the carcinogen 4-nitroquinoline-1-oxide (4NQO) developed premalignant oral lesions and, subsequently, OSCC. Immunohistochemical analyses showed that these 4NQO-induced lesions and OSCC both overexpressed the tumor antigens epidermal growth factor receptor, RAGE and, to a lesser extent, MUC1. Because there was shared overexpression of tumor antigens on premalignant oral lesions and OSCC, dendritic cells pulsed with lysates of 4NQO-induced premalignant lesion cells were tested in vitro and in vivo for their capacity to stimulate T-cell reactivity to premalignant lesion cells and to OSCC. Spleen cells that were sensitized during coculture or in vivo with premalignant lesion-pulsed dendritic cells were cytolytic toward both premalignant lesion cells and OSCC, and secreted increased levels of interferon -gamma in response to challenge with premalignant lesion cells or OSCC as compared with spleen cells that were sensitized with keratinocyte-pulsed dendritic cells. Levels of CD8+ Tcells and interferon-gamma release were also increased in lesions of mice that were vaccinated with premalignant lesion-pulsed dendritic cells. The mice that were vaccinated against premalignant lesions were also more resistant to OSCC challenge. These studies show the feasibility of using premalignant oral lesions to stimulate immune reactivity against both premalignant oral lesions and

Although most histological diagnoses are made with relative ease and with great specificity and reproducibility, there is a subset of cases in which a specific and reproducible diagnosis is difficult or even impossible to render. In the melanocytic system, these cases can be divided into two broad categories. The first category, 'superficial atypical melanocytic proliferations of uncertain significance' (SAMPUS), includes predominantly junctional melanocytic proliferations, and melanocytic proliferations that are confined to the epidermis and papillary dermis, without evidence of tumorigenic proliferation or mitotic activity there. The prognosis for cure of these lesions is excellent if they are completely excised. Such lesions may include, for example, dysplastic naevi, Spitz naevi or pigmented spindle cell naevi with a few atypical melanocytes above the dermal-epidermal junction, or with greater than average cytological atypia, or with mitoses, where the differential diagnosis of melanoma in situ is difficult or impossible to rule out. The other category, 'melanocytic tumours of uncertain malignant potential' (MELTUMP), is comprised of melanocytic proliferations that form tumours in the dermis, and are therefore potentially capable of metastasis. Examples of such lesions may include atypical Spitz naevi, deep penetrating naevi, possible naevoid melanomas, or cellular blue naevi, where because of increased mitotic activity or cytologic atypia, a diagnosis of invasive or tumorigenic melanoma cannot be ruled out. In managing such lesions, we follow two main principles. The first is to manage each lesion with therapy designed to be adequate for management of the most significant consideration in the differential diagnosis. The second principle is to make clinicians and patients specifically aware of the diagnostic difficulty in their lesion, so that management can be undertaken on a true informed consent basis.

Purpose of Review: Laryngeal carcinogenesis is a multistep process with premalignant lesions progressing to invasive carcinoma over a period of years. The approach to these advanced premalignant lesions has always been early diagnosis and treatment to prevent further progression. Unfortunately, with the current means of diagnosis and a lack of consensus regarding treatment of these lesions, the incidence of advanced laryngeal malignancies continues to rise. The purpose of this article is to review the most recent contributions to the literature regarding diagnosis and management of advanced laryngeal premalignant lesions., Recent Findings: The current literature focuses on several new diagnostic procedures to improve early detection of high-risk laryngeal lesions. These procedures include autofluorescence endoscopy, compact endoscopy, and topical 5-aminolevulinic acid. One large long-term study suggests an aggressive surgical approach in the treatment of advanced laryngeal premalignancies to decrease the incidence of malignant transformation. The preliminary results of chemoprevention trials as well as potential new biomarkers are discussed., Summary: There are several new promising procedures that may have an impact on the early diagnosis of laryngeal precursor lesions. In addition, we are gaining knowledge about the molecular events occurring along the continuum of laryngeal carcinogenesis. This will hopefully allow the identification of additional biomarkers and future targets for chemoprevention.

Nephrogenic rests are the consequence of residual metanephric tissue in a fully developed kidney. They usually occur along the perimeter of a mature renal lobe (i.e., perilobar), within the lobe itself (i.e., intralobar), or both (i.e., combined). Nephrogenic rests can be grossly obvious or microscopically discrete. Nephroblastomatosis designates nephrogenic rests that are multifocal or diffuse, and implies more extensive disease. Universal (panlobar) nephroblastomatosis denotes complete replacement of the renal lobe by nephrogenic tissue. The fate of nephrogenic rests and nephroblastomatosis varies and includes obsolescence, sclerosis, dormancy, hyperplasia, or neoplasia. Evidence strongly suggests that neoplastic transformation of nephrogenic rests results in Wilms' tumor (nephroblastoma). Nephrogenic rests almost always occur in the setting of Wilms' tumor; perilobar rests show a strong association with synchronous bilateral Wilms' tumors, whereas intralobar rests are more strongly associated with metachronous tumors. Genetic studies have shown that nephrogenic rests often share many of the same chromosomal defects as Wilms' tumor, which provides further evidence that they are precursors to nephroblastoma. Thus, nephrogenic rests are recognized as clinically significant entities requiring adequate detection and close surveillance. Heightened awareness regarding the clinical relevance of nephrogenic rests and nephroblastomatosis (1) has led to improved detection of these precancerous lesions, (2) fostered more intensive investigation into their biologic behavior, and (3) initiated in-depth discussions about potentially new treatment regimens. The pathologists' ability to identify and detect nephrogenic rests has benefited from the more efficient Beckwith classification. Radiologists have deployed high-resolution radiologic/imaging modalities to improve detection of nephrogenic rests in situ. Clinicians and surgeons are more aware of the impact that nephrogenic rests have upon patient management. Despite this progress, more data is needed to further define these lesions.

Lung cancer is a leading cause of cancer death worldwide; however, despite major advances in cancer treatment during the past two decades, the prognostic outcome of lung cancer patients has improved only minimally. This is largely due to the inadequacy of the traditional screening approach, which detects only well-established overt cancers and fails to identify precursor lesions in premalignant conditions of the bronchial tree. In recent years this situation has fundamentally changed with the identification of molecular abnormalities characteristic of premalignant changes; these concern tumour suppressor genes, loss of heterozygosity at crucial sites and activation of oncogenes. After considering the morphological modifications that occur in premalignant lesions of the bronchial tree, we analyse the alterations occurring in a series of relevant genes: p53 and its functional regulation by MDM2 and p14ARF, p16INK4, p15INK4b, FHIT, as well as LOH at important sites such as 3p, 8p, 9p and 5q. Activation of oncogenes is considered for K-ras, the cyclin D1, the heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1), and finally the c-myc oncogene. The expression of c-myc is influenced strongly by the presence of growth factors (GFs), among which EGF is of prime importance, as well as its receptor coded for by the c-erbB-2 oncogene. Basic knowledge at the molecular level has extremely important clinical implications with regard to early diagnosis, risk assessment and prevention, and therapeutic targets. The novel techniques for early diagnosis and screening of premalignant lung lesions, such as fluorescence bronchoscopy, endobronchial ultrasound, spiral computed tomography combined with precise spatial localization techniques, should basically change the approach to the problems raised by this disease and allow for an increased discovery rate of incipient lesions. Sequential applications will lead to the identification of individuals/populations at high risk, while the availability of accurate 'intermediate end points' will enable the effects of preventive trials to be monitored. Finally, the same molecular abnormalities may serve as 'starting points' for innovative treatments designed to restore the altered functions to normality. Recent developments in our knowledge and understanding of the molecular genetic abnormalities in premalignant lung lesions open an era of hope.

The human genome project has revolutionized technology for the study of DNA. Several of this year's papers have applied these techniques to the study of testicular cancer, especially the use of double-fluorescence in situ hybridization to identify the germ cell tumor marker isochrome 12p in tissue sections, and loss-of-heterozygosity studies to demonstrate a candidate suppressor gene on the long arm of the same chromosome that may be a ligand for the c-kit protooncogene. The report of a solitary case of a patient with a tumor (in a solitary testis) who was treated by partial orchiectomy and then fathered two children emphasizes the need for more information on fertility of patients with carcinoma in situ before the highly effective low-dose radiation to the testis can be accepted. The confirmation of the occurrence of acute myeloid leukemia as a late effect of etoposide and stomach cancer as a late effect of radiotherapy for stage I seminoma has drawn attention to the need to reduce treatment in good-risk patients. Results of trials substituting cisplatin with carboplatin and a trial eliminating bleomycin are particularly disappointing, and the 10% lower cures with the experimental regimen in these studies is an object lesson of the risks involved in such studies. Two other issues that continue to be debated include the increasing recognition of the value of lactate dehydrogenase-1 for identifying poor-risk patients, and the benefits of referral to a unit specializing in testicular cancer. There is an increasing trend to use high-dose chemotherapy for previously untreated patients who have poor risk factors. who have poor risk factors.

BE is a disorder that occurs in children likely as a consequence of prolonged GE reflux of gastroduodenal contents. It usually presents with complications of GE reflux, but it also may be relatively silent in childhood and then present with adenocarcinoma in childhood or present in adulthood. Although seldom recognized in children until relatively recently, it is being diagnosed with greater frequency but not always accurately. The diagnosis of BE can be made with certainty only if landmarks are carefully documented, and a detailed histologic map is made from multiple, large biopsies taken under direct vision at endoscopy; the diagnosis should be reserved for those patients where Barrett's specialized epithelium i.e., goblet cell metaplasia, is present. BE is a diagnosis that should be made with thorough documentation because of the implications for regression, cancer, and the need for follow-up and endoscopic biopsy surveillance. For treatment of complications and because there may be a chance for regression of a young (i.e., childhood) lesion, antireflux surgery or indefinite aggressive acid suppressing medical therapy is required. Because bile reflux may have a pathogenic role in BE, and because of the proven benefits of surgery in producing partial regression and prevention of dysphagia and cancer in some patients, the author's preference at present is for surgery. For children who are poor candidates for surgery, long-term omeprazole should be used (159). Adenocarcinoma does occur in childhood as a complication of BE. Because it can be recognized early, regular surveillance of children with bona fide BE is advisable.

A better understanding of the natural history of pigmented lesions has recently led to a more conservative surgical approach to the management of certain congenital, dysplastic, and other acquired melanocytic nevi. The treatment of primary melanoma is still based almost exclusively on the thickness of the primary lesion. Recent data showed that a surgical margin of 1 cm is appropriate treatment of most thin melanomas (1 mm or less in Breslow thickness), whereas thicker lesions may be removed with a surgical margin of 2 to 3 cm without adversely affecting the rate of local recurrence or patient survival. These recommendations are guidelines only and may be modified by the anatomic site and histologic subtype of tumor. The value of prophylactic lymph node dissection in the management of primary melanoma is still debated and awaits the results of randomized, prospective studies.

In contrast to several retrospective studies reporting an increased risk of endometrial cancer during the mid-1970s, especially in estrogens.gen-treated postmenopausal women, the number of cancers at Wilford Hall USAF Medical Center has steadily declined despite continued estrogen use. In a 4-year study from 1975 to 1978, there were 17 adenocarcinomas of the endometrium during 10,872 patient-years of observation, for an overall annual incidence of 156.4:100,000 women. The highest incidence of endometrial cancer (359.1:100,000) was found in those women using estrogens alone. The lowest incidence of cancer was observed in the estrogen-progestogen users (56.4:100,000) and was significantly lower (P less than .01) than that found in the estrogen users. The incidence of corpus malignancy in the estrogen-progestogen users was also significantly lower (P less than .05) than that observed in the untreated women (248.3:1000,000). The progestogen challenge test has been devised to identify postmenopausal women at greatest risk for adenocarcinoma of the endometrium. It is concluded that the use of this test will reduce the risk of endometrial cancer in both estrogen-treated postmenopausal women and women with increased endogenous estrogens.